2,551 research outputs found
HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer
No full textBackground: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC
De zee-straet van 's Graven-hage op Schevening /
No full textEngraved plate by Romeyn de Hooghe."Steen-wegh vanden Haghe op Schevening": p. 41-53."Op de zee-straet van den heere van Zuylichem"--4 p. interpolated into signature A.Signatures: A⁴(A1+*²) B-G⁴.Mode of access: Internet.Library's copy bound with: Koren-bloemen : nederlandsche gedichten / van Constantin Huygens ridder ... In 's Graven-Hage : By Adriaen Vlack, 1658. (93-b13650
Letter from Dan Hage to James B. Finley
No full textDan Hage has been advised by his presiding elder to write to Finley for help in locating a man named Thomas Wilson Gibson, who once lived in Chillicothe or near there in Perry County. A 1,000 acre piece of land bought in 1795 by Guyan Grier was left to Gibson and never claimed. Hage wishes the land given to Gibson if he can be found, or to buy it from him, part of it for himself and part of it for Page\u27s Meeting House. Page had left land to the church, but a Mr. Taylor had unscrupulously bought the land (or at least part of it) for 20. If Hage can locate Gibson or his heirs and buy this other land from them, he will give back to the church what Taylor took from it (from the Page Estate), as the Gibson Estate lies near Page\u27s Meeting House. Abstract Number - 153https://digitalcommons.owu.edu/finley-letters/1151/thumbnail.jp
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A dynamic transcriptome technique for transcriptional profiling and gene regulatory network involving the helicase antigen (HAGE)
No full textIncreased knowledge into the molecular pathways disrupted in tumours has led to the development of various therapies that can target specific mediators of these cascades. Such therapies have proven successful in patients or demonstrate significant potential for clinical use. However, this better understanding is undermined by the continued prevalence of cancer and the limitations of these drugs. Therefore, it is possible signalling networks could be influenced by as yet unknown molecules or known mediators with function that have not yet been described. As a result of this, work must continue to improve knowledge yet further to allow the design of novel therapies to aid in the treatment of cancer patients. In the present study, work was performed on the helicase antigen (HAGE), a cancer/testis (CT) antigen and DEAD-box protein found to be present in numerous types of malignancy. As with the majority of CT antigens, the role of HAGE remains unclear. In this instance, studies were carried to discover the function of HAGE in malignant cells. Preliminary in vitro proliferation studies following HAGE gene knockdown or cDNA transfection strongly indicated an association between HAGE expression and increased tumour cell proliferation. This was supported by results gained from in vivo work performed within an immuno-compromised murine model.
Expression profiling analysis of data gained from using the Genechip oligonucleotide microarray platform found significant changes to genes linked not only with proliferation but other cell processes altered during tumorigenesis. Confirmation using real-time qPCR suggested change in expression of certain genes could be recognised in other HAGE-expressing tumour cell lines. This analysis also indicated a possible interaction between HAGE and the oncogene N-RAS. Subsequent genetic and protein studies implicated HAGE acting upstream of N-RAS, markedly increasing the N-RAS level in cells. Very preliminary work has begun to demonstrate a role not just in proliferation, but in immune escape, apoptosis inhibition and metastasis, all processes potentially influenced by the RAS oncogenes. The data presented here strongly supports the hypothesis of HAGE having a significant role in malignant biology and warrant continued investigation to further confirm its role in cancer and possibly use as a target for malignancy in the future
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HAGE, a novel cancer/testis antigen with strong potential as a target for immunotherapy against cancers
No full textSince van der Bruggen et al. (1991) first identified specific human tumour antigens of the MAGE family, numerous potential immunotherapeutic targets have been discovered, often belonging to the so-called cancer/testis (CT) gene family. In a search for novel epitopes from potential tumour target antigens, HAGE, a CT antigen, has been studied. It was first identified in a sarcoma and has since been reported in several carcinomas and leukaemias at the mRNA level only. This study proposed to investigate HAGE as a potential target for immunotherapy in a murine tumour model. HAGE mRNA was found to be expressed in a small proportion of carcinomas, some melanomas and in a strong proportion of chronic myeloid leukaemias as compared to normal tissues, which do not express HAGE with the exception of testis. HAGE protein levels were also confirmed on tissue sections and in cell lines in order to rule out any post-transcriptional modifications. Furthermore, HAGE has been previously described as member of the DEAD-box family of ATP-dependent RNA helicases but very little is known about its actual function. RNA helicases are involved in various steps of RNA metabolism and their over-expression has often been linked with tumorogenesis. Using a combination of silencing and transfection experiments, HAGE was proven to be critical for tumour cell proliferation
The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1
No full textThe tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro
Frequent expression of HAGE in presentation chronic myeloid leukaemias
No full textCancer testis (CT) antigens provide attractive targets for cancer-specific immunotherapy. Although CT genes are expressed in some normal tissues, such as the testis and in some cases placenta, these immunologically protected sites lack MHC I expression and as such, do not present 'self' antigens to T cells. To date, CT genes have been shown to be expressed in a range of solid tumours, but rarely in haematological malignancies. We have extended previous studies to investigate the expression of a comprehensive range of CT genes (MAGE-A1, -A3, -A6, -A12, BAGE, GAGE, HAGE,LAGE-1, NY-ESO-1 and RAGE) for their expression in a cohort of acute and chronic myeloid leukaemia patient samples. CT expression was not detected in 20 normal bone marrow or peripheral blood stem cell samples. In acute myeloid leukaemia (AML) nine of the 26 (35%) samples analysed expressed one or more of the CT genes with six of the samples (23%) expressing HAGE. In chronic myeloid leukaemia (CML) 24 of 42 (57%) presentation chronic myeloid leukaemia (CML) patient samples expressed one or more CT antigen with 23 expressing HAGE. We have shown that HAGE is frequently expressed in CML, and to a lesser extent in AML patient samples. This is the first demonstration of HAGE gene expression in myeloid leukaemia patients and the frequent expression of HAGE at disease presentation opens up the possibility of early immunotherapeutic treatments
[News Clip: Wadih El Hage]
No full textB-roll video footage from the KXAS-TV/NBC station in Fort Worth, Texas, to accompany a news story about the bombing of a building involving Wadih El Hage
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[News Clip: Wadih El Hage]
No full textB-roll video footage from the KXAS-TV/NBC station in Fort Worth, Texas, to accompany a news story about the bombing of a building involving Wadih El Hage
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